Concomitant EGFR mutation and EML4-ALK gene fusion in non-small cell lung cancer. Print this page / d( L9 X6 l* Q* R
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Molecular Targets
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6 A" n9 T1 B( r+ y3 DTumor Biology # Y9 M: a/ r3 m+ I" [
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Meeting:
h! g8 t, ]4 {$ t% f* k0 L( j2011 ASCO Annual Meeting
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Session Type and Session Title:- }) B. z+ h9 I" h c& Z ?
Poster Discussion Session, Tumor Biology
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10517
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Citation:
0 K9 S+ Q" z0 ?% y3 gJ Clin Oncol 29: 2011 (suppl; abstr 10517) . T3 Q$ l. E! M& c" p- y* ]* _
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Author(s):
# [; C, V$ [$ G1 g. rJ. Yang, X. Zhang, J. Su, H. Chen, H. Tian, Y. Huang, C. Xu, Y. L. Wu; Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, China; Guangdong Lung Cancer Institute, Medical Research Center of Guangdong General Hospital, Guangzhou, China; Guangdong Lung Cancer Institute, Guangzhou, China; Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, China 0 H! i. j& t1 p9 j/ ~& z
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6 z0 Y9 m8 l5 D+ IAbstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy are designated with a caret symbol (^) here and in the printed Proceedings.
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$ m3 }( @% v3 j, |3 J8 q. R& O8 ~% jAbstract Disclosures
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. P3 o1 H9 S, G; H; Q) C' Z1 SAbstract:
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/ d+ m# B0 U3 T% S+ _Background: The fusion of the anaplastic lymphoma kinase (ALK) with the echinoderm microtubule-associated protein-like 4 (EML4) and epidermal growth factor receptor (EGFR) mutations are considered mutually exclusive. Advanced non-small cell lung cancer (NSCLC) patients with EML4-ALK did not benefit from EGFR tyrosine kinase inhibitors (TKIs). Methods: Multiplex reverse transcriptase-polymerase chain reaction (RT-PCR) followed by sequencing was performed for EML4-ALK fusion status detection. EGFR and KRAS mutations were determined by direct DNA sequencing. Positive results of EML4-ALK fusion were also confirmed by RACE-coupled PCR sequencing. Results: From April 2010 to January 2011, 412 patients (398 with NSCLC; 14 with SCLC) were tested for mutation status of EGFR, KRAS and EML4-ALK respectively. Frequency of EML4-ALK fusion was 10.6% (42/398) in NSCLC patients. No patients with SCLC were found to have positive EML4-ALK fusion. Frequency of concomitant EGFR and EML4-ALK gene mutations was 1.0% (4/398) in NSCLC patients, and their variants of EML4-ALK gene mutations were Variant 1 (3 patients) and Variant 6 (1 patient); being never smokers, all of them were diagnosed with advanced (3 with stage †W and 1 with stage IIIB) adenocarcinoma harbouring wild type KRAS. Two female stage †W patients with double gene mutations (1 with L858R and Variant 1; 1 with exon19 deletion and Variant 6) received first-line gefitinib which is one kind of EGFR TKIs and achieved partial response. Conclusions: Though being rare events, NSCLC patients harbouring concomitant EGFR mutation and EML4-ALK gene fusion are sensitive to first-line EGFR TKIs. Whether they could also benefit from ALK inhibition after failure to EGFR TKIs warranted further investigation.
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